Shilpa Gupta, MD: Immunotherapy is approved for platinum-refractory disease—that is, patients who progress after receiving cisplatin or carboplatin. The JAVELIN Bladder 100 trial, which looked at maintenance immunotherapy with avelumab, is novel. The concept of switch maintenance was tested—that is, patients who have a response or stable disease at the first-line platinum therapy.
We also did a trial with pembrolizumab as a part of the Hoosier Cancer Research Network study, led by Dr Matt Galsky, in which we used pembrolizumab as a switch maintenance strategy. The whole concept is instead of putting patients on surveillance, those who respond to platinum have stable disease after 6 cycles or so; we don’t treat them until they progress. As a part of the studies, patients received immunotherapy early on because we wanted to see if these patients’ outcomes would be improved.
The data from the JAVELIN Bladder 100 show that patients who received immunotherapy maintenance as opposed to best supportive care had a remarkably improved overall survival and progression-free survival. Looking at the data from platinum-refractory setting with immunotherapy, it appears that the earlier use of immunotherapy is better because we are not missing out on patients who may lose out on getting immunotherapy as well.
Jeanny Aragon-Ching, MD: JAVELIN Bladder 100 was a multicenter, international, phase 3, randomized trial of metastatic urothelial cancer patients who received chemotherapy. They received 4 to 6 cycles of platinum-based chemotherapy, so that could have been gemcitabine or cisplatin, or carboplatin with gemcitabine combination. They should have achieved complete response, partial response, or stable disease.
If they progress on the chemotherapy regimens, they would not have been allowed to get randomized. The randomization arm was either maintenance avelumab or best supportive care. Avelumab was given 10 mg/kg every 2 weeks, and there was no limit to how long they were going to get it—until toxicity, perhaps, or progressive disease they continued on with the treatment. The primary end point was overall survival in both the primary analysis, as well as the PD-L1 population of patients.
The population of JAVELIN Bladder 100 is contemporary and relevant in clinical practice. Most patients who have completed or are able to complete chemotherapy are often wiped out. Remember, our bladder cancer patient population tends to be older. By the time they get 4 to 6 cycles of chemotherapy, even though they have good response, a lot of them are having adverse effects from chemotherapy.
In addition, a lot of them may progress after finishing chemotherapy, so a treatment that may be able to consolidate that response would be well received. This is the setting of JAVELIN Bladder 100, and that’s how we are able to translate it into real-world practice. Being able to maintain them on a certain treatment regimen that, hopefully, has no overlapping effects with chemotherapy is really ideal. This is where the switch maintenance approach would really be useful in this population of patients.
Transcript Edited for Clarity